Medicine and Health Sciences Commons^™

Quality-Adjusted Survival In Women With Gynecologic Malignancies Receiving Imrt After Surgery: A Patient Reported Outcome Study Of Nrg Oncology’S Rtog 1203, Andre Konski, Snehal Deshmukh, Ann H Klopp, Anamaria R Yeung, Shannon N Westin, J Spencer Thompson, Desiree E Doncals, Guilherme H C Cantuaria, David P D'Souza, Amy Chang, Vijayananda Kundapur, Dasarahally S Mohan, Michael L Haas, Yong Bae Kim, Catherine L Ferguson, Stephanie L Pugh, Lisa A Kachnic, Deborah W Bruner

Faculty, Staff and Student Publications

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments.

METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along …

Ddx41 Mutations In Patients With Non-Myeloid Hematologic Neoplasms, Fatima Zahra Jelloul, Mark J Routbort, Courtney D Dinardo, Carlos E Bueso-Ramos, Rashmi Kanagal-Shamanna, Beenu Thakral, Zhuang Zuo, C Cameron Yin, Sanam Loghavi, Chi Young Ok, Sa A Wang, Zhenya Tang, M James You, Keyur P Patel, L Jeffrey Medeiros, Andrés E Quesada

Faculty, Staff and Student Publications

No abstract provided.

Neutrophil Cd64 Index As A Good Biomarker For Early Diagnosis Of Bacterial Infection In Pregnant Women During The Flu Season, Lifei Yu, Panpan Cen, Linjian Zhang, Jianfei Ke, Xiangfei Xu, Jiexia Ding, Jie Jin, Jianhang Leng, Yunsong Yu

Faculty, Staff and Student Publications

BACKGROUND: Pregnant women are at high risk of developing febrile illness during the flu season. Early identification of a viral or bacterial infection is crucial in the management of febrile pregnant patients. Neutrophil CD64 (nCD64) has been shown to have more important diagnostic value in sepsis than traditional inflammatory indicators.

METHODS: The pregnant women enrolled were divided into three groups according to disease: influenza A infection, bacterial infection and healthy controls. Peripheral blood CD64, leukocyte, C-reactive protein (CRP), procalcitonin (PCT) and human Th1/Th2-related cytokines levels were routinely measured. The correlation between and diagnostic value of the nCD64 index and other …

Artificial Mirnas Derived From Mir-181 Family Members Have Potential In Cancer Therapy Due To An Altered Spectrum Of Target Mrnas, Sergiu Chira, Cristina Ciocan, Cecilia Bica, George A Calin, Ioana Berindan-Neagoe

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miRNAs are a class of noncoding RNAs with gene regulation properties, and they function as key factors in cell homeostasis. The interaction of miRNAs with their target mRNAs is largely considered to rely on sequence complementarity; however, some evidence indicates that mature miRNAs can adopt diverse conformations with implications for their function. Using the oncogenic miR-181 family as a study model, we suggest that a potential relationship between the primary sequence and secondary structure of miRNAs may have an impact on the number and spectrum of targeted cellular transcripts. We further emphasize that specific alterations in miR-181 primary sequences might …

The Association Of Race And Ethnicity With Severe Maternal Morbidity Among Individuals Diagnosed With Hypertensive Disorders Of Pregnancy, Ashok Krishnaswami, Michael W Rich, Min Ji Kwak, Parag Goyal, Daniel E Forman, Abdulla A Damluji, Matthew Solomon, Jamal S Rana, Deborah M Kado, Michelle C Odden

Faculty, Staff and Student Publications

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 >mmHg) to standard (<140 >mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial.

METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality …

Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit

Faculty, Staff and Student Publications

The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune …

Combining Voltage-Sensitive Dye, Carbon Fiber Array, And Extracellular Nerve Electrodes Using A 3-D Printed Recording Chamber And Manipulators, Curtis L Neveu, Yu Huan, Yuto Momohara, Paras R Patel, Hillel J Chiel, Cynthia A Chestek, John H Byrne

Faculty, Staff and Student Publications

BACKGROUND: The analyses of neuronal circuits require high-throughput technologies for stimulating and recording many neurons simultaneously with single-neuron precision. Voltage-sensitive dyes (VSDs) have enabled the monitoring of membrane potentials of many (10-100 s) neurons simultaneously. Carbon fiber electrode (CFE) arrays allow for stimulation and recording of many neurons simultaneously, including intracellularly.

NEW METHOD: Combining CFE with VSD leverages the advantages of both technologies, allowing for stimulation of single neurons while recording the activity of the entire network. 3-D printing technology was used to develop a chamber to simultaneously perform VSD imaging, CFE array recording, and extracellular recording from individual glass …

Who Is At Risk For New Hepatitis B Infections Among People With Hiv?, John M Sladic, Barbara S Taylor, Mae Thamer, Karen J Vigil, Onkar Kshirsagar, Anna Taranova, Andrew Mccracken, Carmen G Sanchez, Mamta K Jain

Faculty, Staff and Student Publications

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy.

Predicting Severity Of Radiation Induced Lymphopenia In Individual Proton Therapy Patients For Varying Dose Rate And Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations, Lucas Mccullum, Jungwook Shin, Stella Xing, Chris Beekman, Jan Schuemann, Theodore Hong, Dan Duda, Radhe Mohan, Steven H Lin, Camilo M Correa-Alfonso, Sean Domal, Julia Withrow, Wesley Bolch, Harald Paganetti, Clemens Grassberger

Faculty, Staff and Student Publications

PURPOSE: Radiation-induced lymphopenia has gained attention recently as the result of its correlation with survival in a range of indications, particularly when combining radiation therapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo radiosensitivity of circulating lymphocytes and study the effect of RT delivery parameters.

METHODS AND MATERIALS: We assembled a cohort of 17 patients with hepatocellular carcinoma treated with proton RT alone in 15 fractions (fx) using conventional dose rates (beam-on time [BOT], 120 seconds) for whom weekly absolute …

Tp53 Gain-Of-Function Mutation Modulates The Immunosuppressive Microenvironment In Non-Hpv-Associated Oral Squamous Cell Carcinoma, Yewen Shi, Xiaoyong Ren, Shaolong Cao, Xi Chen, Bo Yuan, Fabio Henrique Brasil Da Costa, Alanis E Rodriguez Rosario, Arnoldo Corona, Chieko Michikawa, Ratna Veeramachaneni, Abdullah A Osman, Tongxin Xie, Wenyi Wang, Andrew G Sikora, Jeffrey N Myers, Roberto Rangel

Faculty, Staff and Student Publications

BACKGROUND: TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.

METHODS: Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H …

Tmbim6 Deficiency Leads To Bone Loss By Accelerating Osteoclastogenesis, Sun-Ju Yi, You-Jee Jang, Seokchan Lee, Sung-Jin Cho, Kyuho Kang, Jae-Il Park, Han-Jung Chae, Hyung-Ryong Kim, Kyunghwan Kim

Faculty, Staff and Student Publications

TMBIM6 is an endoplasmic reticulum (ER) protein that modulates various physiological and pathological processes, including metabolism and cancer. However, its involvement in bone remodeling has not been investigated. In this study, we demonstrate that TMBIM6 serves as a crucial negative regulator of osteoclast differentiation, a process essential for bone remodeling. Our investigation of Tmbim6-knockout mice revealed an osteoporotic phenotype, and knockdown of Tmbim6 inhibited the formation of multinucleated tartrate-resistant acid phosphatase-positive cells, which are characteristic of osteoclasts. Transcriptome and immunoblot analyses uncovered that TMBIM6 exerts its inhibitory effect on osteoclastogenesis by scavenging reactive oxygen species and preventing p65 nuclear localization. …

Prmt7 Can Prevent Neurovascular Uncoupling, Blood-Brain Barrier Permeability, And Mitochondrial Dysfunction In Repetitive And Mild Traumatic Brain Injury, Christina H Acosta, Garrett A Clemons, Cristiane T Citadin, William C Carr, Mariana Sayuri Berto Udo, Vesna Tesic, Henry W Sanicola, Anne H Freelin, Jamie B Toms, J Dedrick Jordan, Bharat Guthikonda, Krista M Rodgers, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin

Faculty, Staff and Student Publications

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of …

Blastoid And Pleomorphic Mantle Cell Lymphoma Demonstrate Distinct Clinicopathologic And Genetic Features, Mahsa Khanlari, Huan Mo, Do Hwan Kim, Ali Sakhdari, Ken H Young, Preetesh Jain, Michael Wang, Shaoying Li, Rashmi Kanagal-Shamanna, Roberto N Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

The blastoid (B) and pleomorphic (P) variants of mantle cell lymphoma (MCL) are associated with aggressive clinical behavior. In this study, we collected 102 cases of B-MCL and P-MCL from untreated patients. We reviewed clinical data, analyzed morphologic features using an image analysis tool (ImageJ) and we assessed mutational and gene expression profiles. The chromatin pattern of lymphoma cells was assessed quantitatively by the pixel value. Cases of B-MCL showed a greater median pixel value with lower variation compared with P-MCL, indicating a homogeneously euchromatin-rich pattern in B-MCL. In addition, the Feret diameter of the nuclei was significantly smaller (median …

Whole Blood Resuscitation And Association With Survival In Injured Patients With An Elevated Probability Of Mortality, Jason L Sperry, Bryan A Cotton, James F Luther, Jeremy W Cannon, Martin A Schreiber, Ernest E Moore, Nicholas Namias, Joseph P Minei, Stephen R Wisniewski, Frank X Guyette, Shock, Whole Blood, And Assessment Of Traumatic Brain Injury (Swat) Study Group

Faculty, Staff and Student Publications

BACKGROUND: Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation.

STUDY DESIGN: A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors.

RESULTS: A total …

Individual, Systemic And State Factors Associated With Provider Recommendation Of Hpv Vaccination: Findings From Nis-Teen, 2020, Ikponmwosa Osaghae, Monalisa Chandra, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

The most important determinant of HPV vaccination uptake is healthcare provider recommendation, yet not all eligible patients receive HPV vaccination recommendations. We used data from the 2020 National Immunization Survey-Teen to determine individual, systemic, and state factors associated with provider recommendation of HPV vaccination. A total of 18,534 teens were included, with 81.4% receiving provider recommendations for HPV vaccination. HPV vaccination recommendation was higher among females compared to males (AOR: 1.57; 95% CI: 1.27-1.93), teens who received a well-child exam at 11 or 12 years compared to those who did not (AOR: 2.10; 95% CI: 1.61-2.74), and teens whose mothers …

Gwas-Identified Telomere Length Associated Genetic Variants Predict Risk Of Recurrence Of Hpv-Positive Oropharyngeal Cancer After Definitive Radiotherapy, Peng Sun, Peng Wei, Hongliang Liu, Jia Wu, Neil D Gross, Andrew G Sikora, Qingyi Wei, Sanjay Shete, Mark E Zafereo, Jisheng Liu, Guojun Li

Faculty, Staff and Student Publications

Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP).

Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations.

Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk …

Cardiac Substructure Radiation Dose And Risk Of Late Cardiac Disease In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, James E Bates, Suman Shrestha, Qi Liu, Susan A Smith, Daniel A Mulrooney, Wendy Leisenring, Todd Gibson, Leslie L Robison, Eric J Chow, Kevin C Oeffinger, Gregory T Armstrong, Louis S Constine, Bradford S Hoppe, Choonsik Lee, Yutaka Yasui, Rebecca M Howell

Faculty, Staff and Student Publications

PURPOSE: Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.

METHODS: Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.

RESULTS: The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 …

Rewiring Cancer Drivers To Activate Apoptosis, Sai Gourisankar, Andrey Krokhotin, Wenzhi Ji, Xiaofan Liu, Chiung-Ying Chang, Samuel H Kim, Zhengnian Li, Wendy Wenderski, Juste M Simanauskaite, Haopeng Yang, Hannes Vogel, Tinghu Zhang, Michael R Green, Nathanael S Gray, Gerald R Crabtree

Faculty, Staff and Student Publications

Genes that drive the proliferation, survival, invasion and metastasis of malignant cells have been identified for many human cancers1-4. Independent studies have identified cell death pathways that eliminate cells for the good of the organism5,6. The coexistence of cell death pathways with driver mutations suggests that the cancer driver could be rewired to activate cell death using chemical inducers of proximity (CIPs). Here we describe a new class of molecules called transcriptional/epigenetic CIPs (TCIPs) that recruit the endogenous cancer driver, or a downstream transcription factor, to the promoters of cell death genes, thereby activating their expression. We focused on diffuse …

Durable Control Of Metastases In An Hla-A2+ Patient With Refractory Melanoma After Low-Dose Radiotherapy In Combination With Mage-A4 T Cell Therapy: A Case Report, Kewen He, David S Hong, Danxia Ke, Partow Kebriaei, Tianjiao Wang, Hassan Danesi, Genevieve Bertolet, Carola Leuschner, Nahum Puebla-Osorio, Tiffany A Voss, Quan Lin, Elliot Norry, Paula M Fracasso, James W Welsh

Faculty, Staff and Student Publications

There is no currently approved adoptive cellular therapy for solid tumors. Pre-clinical and clinical studies have demonstrated that low-dose radiotherapy (LDRT) can enhance intratumoral T cell infiltration and efficacy. This case report describes a 71-year-old female patient with rectal mucosal melanoma that had developed metastases to liver, lung, mediastinum, axillary nodes, and brain. After systemic therapies had failed, she enrolled in the radiation sub-study of our phase-I clinical trial exploring the safety and efficacy of afamitresgene autoleucel (afami-cel), genetically engineered T cells with a T cell receptor (TCR) targeting the MAGE-A4 tumor antigen in patients with advanced malignancies (NCT03132922). Prior …

How Reclassification Of Hydrocodone Combination Products Affects Dispensing, Jonah J Stulberg, Lan Vu, Reiping Huang, Salva N Balbale, Phillip Yoo, Phiyen Tra, Leanne N Metcalfe

Faculty, Staff and Student Publications

No abstract provided.

Multidisciplinary Care Of A Large Brain Metastasis In A Patient With Hormone-Receptor-Positive Breast Cancer With Ataxia-Telangiectasia Mutation, Anca Chelariu-Raicu, Sarina A Piha-Paul, Mariana Chavez-Macgregor, Jason Johnson, Raymond Sawaya, Mary Frances Mcaleer, Alissa Nguyen, Audrey Hartnett, Apostolia M Tsimberidou, Funda Meric-Bernstam, Ecaterina E Dumbrava

Faculty, Staff and Student Publications

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARP)i are emerging as standard oncology treatments in various tumor types. The indications will expand as PARPi are being investigated in various breast cancer subtypes. Currently, except for BRCA1/2 mutation carriers with human epidermal growth factor receptor 2 (HER2)-negative breast cancer, there is inadequate identification of predictive biomarkers of response. We present a 57-year-old woman with metastatic breast cancer, hormone-receptor-positive, HER2 negative with a germline ataxia-telangiectasia mutation with a large brain metastasis with clinical benefit to talazoparib. This case report exemplifies the importance of the multidisciplinary management of patients with brain metastases and personalized biomarker …

Maternal Provisioning Interacts With Incubation Temperature To Affect Hatchling Mercury Exposure In An Oviparous Reptile, Josiah M Johnson, Christopher R Smaga, Samantha L Bock, Benjamin B Parrott

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The thermal environment experienced by developing embryos can influence the utilization of maternally provisioned resources. Despite being particularly consequential for oviparous ectotherms, these dynamics are largely unexplored within ecotoxicological frameworks. Here, we test if incubation temperature interacts with maternally transferred mercury to affect subsequent body burdens and tissue distributions of mercury in hatchling American alligators (

Association Of Patient-Reported Health-Related Quality Of Life With Physician-Reported Toxicities In Adolescents And Young Adults Receiving Radiation Therapy For Cancer, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Grace L Smith, Maria C Swartz, Kamaria L Lee, Faraz Afridi, Lauren M Andring, Andrew J Bishop, Jillian R Gunther, J Andrew Livingston, Susan K Peterson, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

PURPOSE: Radiation therapy (RT) may cause toxicities in adolescents and young adults (AYAs, age 15-39 years) with cancer. However, the range of RT-related toxicities in AYAs and the affect on health-related quality of life (HRQOL) has not been well studied. We performed a cross-sectional study in AYAs with cancer who received RT to identify RT-related toxicities and examine their impact on HRQOL.

MATERIALS AND METHODS: A total of 178 AYAs received RT and completed PROMIS HRQOL instruments from 2018 to 2022. Acute and late physician-graded Common Terminology Criteria for Adverse Events RT-related toxicities were extracted and described. Multivariable linear regression …

Statin Use And Chemoradiation In Esophageal Squamous Cell Carcinomas: Ready For Prime Time?, Steven H Lin

Faculty, Staff and Student Publications

No abstract provided.

Single-Cell Transcriptomic Analysis Uncovers Intratumoral Heterogeneity And Drug-Tolerant Persister In Alk-Rearranged Lung Adenocarcinoma, Hoi-Hin Kwok, Huiyu Li, Jiashuang Yang, Junyang Deng, Nerissa Chui-Mei Lee, Timmy Wing-Kuk Au, Alva Ko-Yung Sit, Michael Kuan-Yew Hsin, Stephanie Kwai-Yee Ma, Lydia Wai-Ting Cheung, Luc Girard, Junya Fujimoto, Ignacio Ivan Wistuba, Boning Gao, John Dorrance Minna, David Chi-Leung Lam

Faculty, Staff and Student Publications

No abstract provided.

The Hylefm Gene In Phylefm Of Enterococcus Faecium Is Not Required In Pathogenesis Of Murine Peritonitis, Victoria H Wu, Bryan S Yung, Farhoud Faraji, Robert Saddawi-Konefka, Zhiyong Wang, Alexander T Wenzel, Miranda J Song, Meghana S Pagadala, Lauren M Clubb, Joshua Chiou, Sanju Sinha, Marin Matic, Francesco Raimondi, Thomas S Hoang, Rebecca Berdeaux, Dario A A Vignali, Ramiro Iglesias-Bartolome, Hannah Carter, Eytan Ruppin, Jill P Mesirov, J Silvio Gutkind

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs–DREADD to activate …

Assessing Cocaine Motivational Value: Comparison Of Brain Reactivity Bias Toward Cocaine Cues And Cocaine Demand, Heather E Webber, Jin H Yoon, Constanza De Dios, Robert Suchting, Vincent Dang, Francesco Versace, Charles E Green, Margaret C Wardle, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices (Q₀, essential value [EV], Omax, Pmax, and …

Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From The Integral-Ilcco Cohort Analysis, Chao Cheng, Wei Hong, Yafang Li, Xiangjun Xiao, James Mckay, Younghun Han, Jinyoung Byun, Bo Peng, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne Arnold, Gary Goodman, John K Field, Michael P A Davies, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Meng Zhu, Hongbing Shen, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Paul Brennan, Yong Li, Olga Gorlova, Ivan Gorlov, Christopher I Amos, Integral-Ilcco Lung Cancer Consortium

Faculty, Staff and Student Publications

INTRODUCTION: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer.

METHODS: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls.

RESULTS: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal …

Biochemical And Structural Characterization Of The First-Discovered Metazoan Dna Cytosine-N4 Methyltransferase From The Bdelloid Rotifer Adineta Vaga, Jujun Zhou, John R Horton, Gundeep Kaur, Qin Chen, Xuwen Li, Fabian Mendoza, Tao Wu, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

Much is known about the generation, removal, and roles of 5-methylcytosine (5mC) in eukaryote DNA, and there is a growing body of evidence regarding N6-methyladenine, but very little is known about N4-methylcytosine (4mC) in the DNA of eukaryotes. The gene for the first metazoan DNA methyltransferase generating 4mC (N4CMT) was reported and characterized recently by others, in tiny freshwater invertebrates called bdelloid rotifers. Bdelloid rotifers are ancient, apparently asexual animals, and lack canonical 5mC DNA methyltransferases. Here, we characterize the kinetic properties and structural features of the catalytic domain of the N4CMT protein from the bdelloid rotifer Adineta vaga. We …

Outcomes After Definitive Treatment For Cutaneous Angiosarcomas Of The Face And Scalp: Reevaluating The Role Of Surgery And Radiation Therapy, Alison K Yoder, Ahsan S Farooqi, Cort Wernz, Aparna Subramaniam, Vinod Ravi, Ryan Goepfert, Erich M Sturgis, Devarati Mitra, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

INTRODUCTION: We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA).

METHODS: We conducted a retrospective review of patients treated for CA of the face and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S-XRT). The Kaplan-Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model.

RESULTS: For the 143 patients evaluated median follow-up was 33 months. Five-year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre-2000, and with single modality therapy (SMT). These remained …